tbuckley/cabot-search huggingface dataset:
Sex- and co-mutation-dependent prognosis of patients with <i>SMARCA4</i>-mutated malignancies.
Authors: Minggui Pan, Chen Jiang, Ninah Achacoso, Aleyda V Solorzano-Pinto, Pamela Tse, Jennifer Marie Suga, Sachdev P. Thomas, Laurel A. Habel
Journal: Journal of Clinical Oncology (2023)

e21031 Background: Whether sex and co-mutations impact prognosis of patients with SMARCA4-mutated (mutSMARCA4) malignancies is not clear. Methods: This cohort included patients from Northern California Kaiser Permanente with next-generation sequencing (NGS) performed from August 2020 to October 2022. We used Cox regression modeling to examine the association between sex and overall survival (OS), adjusting for demographics, performance status, Charlson comorbidity index, receipt of treatment, tumor mutation burden (TMB), and TP53, KRAS, CDKN2A and STK11 co-mutations. Results: Out of 9221 cases with NGS performed, 125 cases (1.3%) had a mut SMARCA4. The most common malignancies with a mutSMARCA4 were non-small cell lung cancer (NSCLC, 35.2%), esophageal and stomach adenocarcinoma (12.8%), and cancer of unknown primary (11.2%). The most common co-mutations were p53 (mutp53, 59.2%), KRAS (mutKRAS, 28.8%), CDKN2A (mutCDKN2A, 31.2%) and STK11 (12.8%) mutations. Male patients had substantially worse OS than female patients both among the entire cohort (HR = 1.76, [95% CI .94-3.30]) with a median OS of 3.0 versus 43.3 months ( P &lt; .001), and among NSCLC cohort (HR = 9.72, [95% CI 2.19-43.19]) with a median OS of 2.75 months versus un-estimable ( P = .02). Among the entire cohort, mutp53 versus wtp53 (HR = 2.16, [95% CI 1.06-4.41]) and mutSTJ11 versus wtSTK11 (HR = 3.09, [95% CI 1.10-8.68]) were associated with worse OS. Among NSCLC cohort, mutp53 versus wtp53 (HR = .20, [.03-1.31]) and mutKRAS versus wtKRAS (HR = .13, [.01-1.03]) were associated with better OS, while mutCDKN2A versus wtCDKN2A (HR = 4.38, [1.13-16.9]) and mutSTK11 versus wtSTK11 (HR = 18.1, [95% CI 1.30-251]) were associated with worse OS. Conclusions: Male patients had substantially worse prognosis than female patients, while MutTP53, mutKRAS, mutCDKN2A and mutSTK11 were differentially associated with prognosis among the entire cohort and among NSCLC cohort. Our results, if confirmed, could suggest potentially unidentified mechanisms that underly this sex and co-mutation-dependent prognostic disparity among patients whose tumor bears a mutSMARCA4.
Efficacy and safety of immune checkpoint inhibitor without pemetrexed for first-line maintenance therapy in advanced lung adenocarcinoma.
Authors: Ming Gao, Wenyu Yang, Chunyu Wang, Ting Wang, Fangfang Jing, Fan Zhang, Haitao Tao, Junxun Ma, Yi Hu, Lijie Wang
Journal: Journal of Clinical Oncology (2023)

e21058 Background: Currently, the standard first-line treatment for driver gene-negative advanced lung adenocarcinoma (LUAD) is chemotherapy plus immune checkpoint inhibitor (ICI) therapy followed by pemetrexed and ICI. However, pemetrexed is prone to certain adverse reactions and needs to be pretreated. At present, there is no relevant study on the efficacy between pemetrexed combined with ICI and ICI monotherapy in maintenance treatment. The object of this study is to explore the efficacy and safety of ICI as maintenance therapy in such patients. Methods: The study retrospectively analyzed patients with driver gene-negative advanced LUAD in PLA General Hospital from January 2019 to June 2022. These patients had received pemetrexed and platinum-based chemotherapy combined with ICI for 4-6 cycles. Patients who didn’t progress were subsequently entered into maintenance stage. The primary endpoint was progression-free survival (PFS) and overall survival (OS), and the secondary endpoint was objective response rate (ORR) and safety. Results: A total of 93 patients with advanced LUAD who received first-line chemotherapy combined with ICI were collected, including 39 patients receiving pemetrexed plus ICI of maintenance therapy, 30 patients receiving ICI maintenance therapy, and 24 patients who failed to enter the maintenance treatment. Baseline characteristics of ICI group and pemetrexed plus ICI group were as follows: median age, 61.5 (42~81) years vs. 63 (35~74) years; male, 66.7% (20/30) vs. 79.5% (31/39); Smoking history, 63.3% (19/30) vs. 74.4% (29/39); Brain metastases, 10% (3/30) vs. 23.1% (9/39). ORR was 60.0% (95%CI 42.5-77.5) in the ICI monotherapy group and 69.2% (95%CI 54.7~83.7) in the pemetrexed plus ICI group. By November 30, 2022, the median follow-up time was 19.2 months. The median PFS of the two groups were 15.8 months (95%CI 9.84-21.70) in ICI group and 22.8 months (95%CI 4.57-40.97) in pemetrexed plus ICI group and there was no statistical difference between the two groups (P = 0.50). Neither group achieved OS. The incidence of all grade treatment-related adverse events (TRAEs) was 90.0% (27/30) in ICI monotherapy group and 92.3% (36/39) in pemetrexed plus ICI group. Grade 3/4 TRAEs occurred in 23.3% (7/30) and 23.1% (9/39) of each cohort and no grade 5 TRAE occurred. Conclusions: ICI maintenance therapy without pemetrexed showed great therapeutic efficacy in first-line maintenance stage and can be a feasible regimen in advanced lung adenocarcinoma.
A series of nine newly developed techniques in CT-guided percutaneous lung biopsyPreliminary results from a prospective study.
Authors: Hanxi Zhang, Xiaolu Wang, Xin Lv, Xia Zhou, Baorui Liu, Lifeng Wang, Rutian Li
Journal: Journal of Clinical Oncology (2023)

e21023 Background: CT-guided percutaneous lung biopsy is important for the diagnosis of lung cancer especially in the area of precision medicine. In ASCO 2015, we reported that "Liquid withdraw" technique (to inject small amount of liquid while withdraw of the needle) can prominently reduce incidence of pneumothorax when combined with co-axial technigue in 38 cases. In ASCO 2017, we retrospectively studied 90 patients undergoing CT-guided percutaneous lung biopsy to investigate the role of this technigue in reducing complications and promoting biopsy effectiveness. Based on the above studies, we conducted a prospective study to further evaluate the role of this technique in conjunction with the other eight techniques (Position compensation, Cushion for position adjustment, Skin expansion in advance, Secondary location outside the pleura, Needle core instantaneous replacement, Mutual fix, Simultaneous bleeding arrest, and Cortical displacement) in the precision diagnosis and treatment of lung cancer. Methods: From January 16th, 2018 to October 11th, 2021, a total of 150 CT-guided percutaneous transthoracic biopsy procedures performed in 146 patients were prospectively evaluated. The pathologies and complications secondary to biopsy procedure were analyzed. Pneumothorax and bleeding was graded as mild/very mild, moderate, and severe. All patients were divided into two groups: the lesion depth was &lt; 30mm from the pleura and ≥30mm from pleura. Different complications between the two groups were analyzed using Pearson’s Chi-squared test for categorical values. Results: 148 cases was diagnosed out of 150 biopsies (98.67%), of which 118 cases were malignant (108 cases can be identified which type and source (91.53%), in which 68 cases were adenocarcinoma), 30 cases were benign. Pneumothorax occurred in 27 (18%) cases, among which, 12% were very mild pneumothorax and 6% were mild to moderate pneumothorax. 44 cases (29.33%) happened bleeding, among which, 21.33% could be classified as very mild, while 8% could be classified as mild to moderate. No infection, tumor implantation or aeroembolism observed. There were no statistically significant differences in the incidence of pneumothorax and bleeding at different distances from the pleura( &lt; 30mm vs ≥30mm, P＞0.05). Conclusions: This series of new techniques in CT-guided percutaneous lung biopsy significantly reduced the incidence of pneumothorax and bleeding and were preliminarily proved that can facilitate acquiring more tumor tissue for molecular testing and re-biopsy of lung cancer. Clinical trial information: ChiCTR1800017958 .
Male breast cancer survival data and clinicopathological characteristics: A single-centre experience.
Authors: Vasiliki Tzouda, Dionysia Zouki, Vasiliki Kardara, Panagiotis Gouveris, George Papaxoinis, Ioannis Tourkantonis, Anastasios Grivas, Stamatina G Demiri, Dimitrios Tryfonopoulos
Journal: Journal of Clinical Oncology (2023)

e18837 Background: Male breast cancer represents an uncommon entity accounting for less than 1% of all breast cancers. Although the understanding of biology, clinical presentation and management are evolving, a large knowledge gap still remains. Due to disease’s rarity, there is a significant paucity of data and most clinicians confront male cases by extrapolating from breast cancer in women. In this study we aim to report our institutional experience across a 17-year period about male breast cancer patients treated at the same centre. Methods: Clinical, histopathological, treatment and survival data of male breast cancer patients diagnosed between 2006 and 2022 at Second Department Medical Oncology in Saint Savvas Anticancer Hospital were identified and analyzed. Results: A total number of 24 male breast cancer patients were detected. The median age at diagnosis was 63 years. All participants had invasive ductal carcinoma. None of them presented with metastatic disease, while the majority had stage II disease (62,5%). All, except two cases, underwent mastectomy with either axillary or sentinel lymph node dissection. Regarding hormone receptors, 96% were ER positive and 25% were PR negative, while 79% were negative for HER-2 overexpression. As far as HER-2 low status is concerned, 42% (10 out of 24) were categorized as low expressors. From genetic point of view, data were available only for 9 cases, 2 of which were BRCA-2 mutant. Adjuvant chemotherapy (anthracycline and taxane based mainly) was administered in 75% (18 out of 24) of patients. At the time of last follow up (January 2023), only 5 participants presented disease progression, with metastatic lesions in bones, liver and lymph nodes. The median disease-free survival (DFS) was 48 months. In our cohort 5 deaths were recorded and the median overall survival (OS) was 58,5 months. Conclusions: Male breast cancer is a unique entity that remains understudied. Our institutional data provide a useful overview about this rare disease in Greece. Ongoing effort is required to conduct clinical trials or to include male patients in large, randomized cohorts in order to improve medical care.
A 9-gene signature in circulating tumor DNA based on molecular residual disease detection to predict recurrence of resectable non–small-cell lung cancer.
Authors: Di Lu, Zhouyu Wang, Airong Yang, Zhiming Chen, Zhizhi Wang, Jing Li, Shaobin Li, Kaican Cai
Journal: Journal of Clinical Oncology (2023)

e20579 Background: Molecular residual disease (MRD) status is associated with the recurrence of non-small cell lung cancer (NSCLC) after complete resection. In clinical practice, MRD-positive patients are still uncertain of the specific recurrence time, and may even not relapse. Besides, it remains unclear whether the mutational signatures of circulating tumor DNA (ctDNA) based on MRD detection (ctDNA-MRD) may help predict recurrence. Therefore, we performed this analysis to explore whether the ctDNA-MRD mutational signatures could help predict recurrence, especially in MRD-positive population. Methods: Two investigators independently searched public databases for articles related with MRD in lung cancer published up to July 31, 2022. After screening, raw data from two published studies on resectable NSCLC were analyzed. Gene clusters were established based on the clearance of ctDNA after surgery. Kaplan-Meier and multivariate analyses were performed to find genes (Monitor genes) and clinical variables associated with recurrence-free survival (RFS). Lasso method was used to find recurrence-related genes based on perioperative ctDNA (preoperative and longitudinal ctDNA). Monitor genes and recurrence-related genes were defined as 9-gene signature. The mutational status of Monitor genes and 9-gene signature in perioperative ctDNA, as well as clinical variables, were used to establish prognostic models. The power of the models in distinguishing recurrence was shown as the area under the curve (AUC). Results: Data from 168 patients with at least one somatic mutation detected in tumors were included in the analysis. DNMT3A, EGFR, TP53, KEAP1, NAV3 (Monitor genes), and clinical variables (stage, adjuvant therapy) were factors associated with RFS. The AUC of the model based on Monitor gene mutations in perioperative ctDNA was 0.774, and the AUC reached 0.807 when clinical variables were included. The AUC of the models based on clinical variables, 9-gene signature (Monitor genes, KRAS, NTRK3, RPL5, and SOX2) in perioperative ctDNA for predicting the recurrence in the overall population and MRD-positive population were 0.840 and 0.832, respectively. Conclusions: This analysis reveals that perioperative ctDNA mutational signatures are helpful to predict postoperative recurrence, so it is necessary to pay attention to the specific gene mutations in ctDNA-MRD. [Table: see text]
Is aggregate use of published case reports as a viable option for augmenting pharmacovigilance? An applied example of pembrolizumab-related adverse events in patients with non-small cell lung cancer receiving first-line treatment.
Authors: Suad Khabbaha, Sarah Carder Dempsey, Aranka Anema, Sonal Singh, Kristian Thorlund
Journal: Journal of Clinical Oncology (2023)

e18840 Background: Pharmacovigilance suffers from considerable underreporting, and causality is rarely confirmed. We aim to examine the validity of the aggregate use of published case reports as a viable option for augmenting pharmacovigilance. We explore the setting of first line pembrolizumab treatment for non-small cell lung cancer as safety signals in this cohort are relatively well documented and because drug-related adverse events are more easily confirmed with no previous drug treatments. Methods: We compared immune-related adverse event rates (Any and Severe) associated with pembrolizumab from three select first non-small lung cancer KEYNOTE clinical trials (024, 042, and 189) to clinician confirmed pembrolizumab-related adverse event rates from a synthetic cohort case report data from a matching population. The latter were retrieved from the OpenCaseTM database and included 126 non-small cell lung cancer patients, of which 110 had received pembrolizumab monotherapy and 16 pembrolizumab in combination with a platinum-based chemotherapy regimen. Baseline characteristics with respect to age, sex, smoking history, non-drug treatment history, PD-L1 tumor proportion score, and key genetic markers (e.g. EGFR, ALK) were acceptably similar (results will be presented in a table). Results: In the synthetic cohort of case reports, Immune-related adverse events, which were clinician confirmed to be related to pembrolizumab, occurred in 86/126 (68.2%). Life threatening and severe treatment-related AEs were 7.4% and 65% respectively. These were substantially higher than reported in clinical trials 8.0%-9.7% experienced severe immune-related events. The majority of the most frequently occurring immune-related AEs in the KEYNOTE trials had similar reported proportions to the case reports. For example, hypothyroidism (any grade) ranged from 6.7% to 9.1% in the KEYNOTE trials compared to 4.9% among the case reports, and pneumonitis (any grade) ranged from 4.4% to 12.0% in the trials compared to 5.5% in the case reports. Other events such as myositis, type 1 diabetes, liver dysfunction, kidney injury, and colitis were frequent in the cohort of case reports (3.1%-7.9%), but rare or unreported in all KEYNOTE trials (0.0%-2.2%). Conclusions: Overall, adverse event rates in the synthetic cohort of case reports were either similar or higher than observed in clinical trials of matching populations. This observation provides rationale for utilizing case reports in pharmacovigilance practice, specifically for rarer events.
Real world data on immunotherapeutic outcomes in solid tumours.
Authors: Vijay Kumar Srinivasalu, Ravi Sekhar Patnaik, Raden Mas Jeffri bin Raden Mas Ismail, Haji Zulkhairi Bin Haji Mohamad, Dr. Shir Kiong Lu, Dato Seri Laila Jasa Dr. Babu Sukumaran
Journal: Journal of Clinical Oncology (2023)

e18785 Background: Defined as “the new kid on the blocks” in the field of medical oncology, Immunotherapy has paved the way in the armamentarium of cancer therapeutics literally in every cancer subtype. There are various biomarkers approved for considering immunotherapy, but none have been reliable. We aim to assess the response rate, PFS, OS, and clinical characteristics of patients who received immunotherapy for treatment in advanced or metastatic solid tumours. Methods: A retrospective study of all patients who were treated with immunotherapy at The Brunei Cancer Center, PJSC between December 2019 – February 2022 was included with a median follow-up of 6 months from the last dose of immunotherapy. Results: A total of 212 patients were included with Pembrolizumab 66% (n = 140), Nivolumab 24% (n = 51), Atezolizumab 8.4% (n = 18), Durvalumab 0.9% (n = 2), and Ipilimumab + Nivolumab 0.4% (n = 1). The median age was 46 years (range 31-78 years) with a female preponderance of 62%. The median number of cycles were 4.5 per patient (range 0-41). Lung cancer 29.7% (n = 63, adenoca-40, squamous-10, adenosquamous-2, SCLC-11), GI tumours 19.3 (n = 41, HCC-17, Stomach-15, MCRC-7, Pancreas-2), GU tumours 12.7% (n = 27, RCC-19, Bladder-7, Penis-1) and Head and neck tumours 9.9% (n = 21, HNSCC-13, NPC-8). On biomarker analysis for initiation of immunotherapy, PDL-1 + on IHC (either by CPS or TPS) was noted in 88 patients, TMB &gt; 10 in 22, and MSI-H in 4 patients. The ORR in this study was 35.3% (CR-10, PR-29, and SD-36). Sixty patients received less than 3 cycles and were not included in the analysis. Disease progression (27), worsening ECOG performance status (14), and IRAEs (19) were the common reasons for discontinuation of these drugs. On ITT analysis, the ORR was 51.3%. The median duration of response is 12.5 months in responders (range 6-31 months). The Median PFS was 4.9 months (95% CI: 1.78-8.21) and the median OS was 7.1 months (95% CI: 8.14-17.85). On univariate analysis for determinants of better PFS, pretreatment NLR &gt; 4 was associated with improved survival (p = 0.001) and presence of co-mutations, low TMB &lt; 5 and younger age &lt; 45 was associated with inferior survival. Conclusions: Pretreatment NLR &gt; 4 can be used as an indicator of response to immunotherapy in the clinics. Benefits of immunotherapy are not universal, best responses were noted in NSCLC, Bladder, and RCC. Identification of novel predictive biomarkers would improve clinical outcomes in solid tumours.
Propensity score matched analysis of major adverse cardiac events in patients with localized prostate cancer receiving short term vs long term ADT.
Authors: Ye Yuan, Gavin Hui, Saurabh Gombar, Nima Aghdam
Journal: Journal of Clinical Oncology (2023)

12096 Background: ADT is often used with radiation for dose-intensification in intermediate-risk prostate cancer (PrCa). ADT includes gonadotropin-releasing hormone (GnRH) agonists, often started with antiandrogens to prevent the initial surge in serum testosterone as well as GnRH antagonists. Studies have reported associations of ADT with increased risks of cardiovascular events. This is thought to be related to atherosclerosis, dyslipidemia and insulin resistance. Therefore, there is an opportunity to individualize ADT use to balance risk of PrCa specific outcomes with risk of MACE. To address this, we assessed whether there is a difference in major adverse cardiac events (MACE) between ST-ADT ( &lt; 6 months) or LT-ADT ( &gt; 6 months) in patients with localized PrCa. Methods: A nationally representative EHR-derived dataset was queried for patients with at least 90 days of longitudinal records and 90 days of continuous follow up. The inclusion criteria was a diagnosis of PrCa based on standardized diagnoses codes (ICD9 and ICD10). Patients who had a history of MACE (defined as combination of diagnosis and procedure codes associated with CAD, MI, unstable angina, CABG, PCI, catheterization) metastases, PSA above 10ng/mL, imaging for metastatic PrCa, or having received abiraterone or docetaxel within 3 months of inclusion were excluded. Patients were defined as receiving ADT if they received leuprolide, goserelin, bicalutamide, triptorelin, degarelix, flutamide, or nilutamide. The primary outcome of risk of any new MACE was compared between arms with Cox proportional hazards regression. Secondary outcomes including 10 year rates of new diagnoses of CAD, metastases, and new heart procedures were compared between arms with the Chi-square test. Significance was set at a two sided p-value of 0.05. All analyses were performed without matching, with age and gender matching, and high dimensional propensity-score matching (hdPS) using R version 4.05. Results: We identified 1209 patients with local PrCa and no prior MACE or use of abiraterone or docetaxel within 3 months of diagnosis. 385 patients received ST-ADT and 824 received LT-ADT. Baseline characteristics were comparable between the two arms with similar ages, and comorbidity scores. There was no significant difference in metastatic recurrence between arms in hdPS-matched analysis HR 0.95 [0.64-1.38] p = 0.8. There was also no significant difference in the composite endpoint of MACE HR 1.42 [0.86-2.36] p = 0.173. More patients in the LT-ADT arm had new CAD, which was significant after hdPS-matched analysis OR 1.84 [1.07-3.14], p = 0.024. Conclusions: In a national dataset analysis of patients with local PrCa and no history of MACE or abiraterone or docetaxel within 3 months of diagnosis LT-ADT was associated with increased odds of CAD but there was no difference in the composite endpoint of MACE or metastatic recurrence.
Agranulocytosis secondary to cancer chemotherapy and association with higher in-hospital mortality in patients with central line insertion during hospital stay.
Authors: Mohamed Zakee Mohamed Jiffry, Felipe Carmona-Pires, Nkechi Okam, Jonathan Vargas, Mohammed Aimal Ahmed-Khan, Kayvon Moin, Meagan Josephs
Journal: Journal of Clinical Oncology (2023)

e18777 Background: Agranulocytosis secondary to cancer chemotherapy (ASCC) remains a leading cause of morbidity and mortality. Central line associated bloodstream infections (CLABSI) are also particularly prevalent in these populations and may portend a poorer outcome. Our study serves to investigate the relationship between patients with agranulocytosis secondary to cancer chemotherapy and insertion of a central venous catheter (CVC) with respect to in-hospital mortality. Methods: We utilized the National Inpatient Survey 2019 database. We utilized ICD-10 CM codes to identify ASCC and other medical comorbidities. We utilized ICD-10 PCS codes to identify CVC insertions. Multivariate logistic regression was utilized to study the effect of CVC insertion on in-hospital mortality. Results: In patients with ASCC, CVC insertion was associated with a higher in-hospital mortality (unadjusted: 11.9% vs 1%, p &lt; 0.001, adjusted OR 19.27, 95% CI 5.84 – 65.6, p &lt; 0.001) adjusted for baseline characteristics and other comorbidities. Patients in the study cohort who were older than 70 years of age also had a higher in-hospital mortality relative to younger age groups (adjusted OR 2.31, 95% CI 1.04-5.13, p &lt; 0.039). Conclusions: In patients with ASCC, CVC insertion during the hospitalization is associated with a higher in-hospital mortality.